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The role of Rac1 and Rac3 in cortical interneuron development

Objectif

GABAergic interneurons play important roles in cortical function and provide the main source of inhibition to cortical microcircuits. Impaired interneuron function results in severe neurodevelopmental disorders such as schizophrenia, epilepsy and autism. Although recent studies have uncovered some of the molecular mechanisms underlying interneuron development, the intracellular components involved are still unknown. Our proposed work, aims to elucidate the role of specific signalling cascades during birth, migration and specification of interneurons, and thus shed light on the intracellular machinery that regulates their proper development.
Rac proteins integrate multiple extracellular signals and are required for many processes in diverse cell types, including cytoskeleton organization, vesicle trafficking, transcription, cell cycle progression, and apoptosis. We are interested in elucidating the roles of Rac1 and Rac3 specifically in MGE-derived interneurons, a population that comprises the majority of cortical interneurons. We have used conditional Rac1 deficient mice (specifically in the MGE) combined with Rac3 null mice and we found that 50% of MGE derived GABAergic interneurons fail to migrate and populate the cortex. MGE-derived interneurons missing both Rac proteins show an even more severe defect (80%). The aim of this proposal is to elucidate the mechanism of Rac1 and 3 action in interneuron development by assaying for: a) the polarity and the involvement of actin/microtubule dynamics in Rac deficient interneurons, b) the nature of the defect in interneuron progenitors as it concerns cell cycle behaviour c) the individual role of each of the two Rac proteins and the involvement of downstream effectors of the Rac pathway and d) the functional properties of interneurons.
The experiments designed combine molecular genetics, imaging, cellular and biochemical assays to reveal the mechanism of action of these intracellular mediators of interneuron development

Appel à propositions

FP7-PEOPLE-2010-RG
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Coordinateur

IDRYMA TECHNOLOGIAS KAI EREVNAS
Contribution de l’UE
€ 45 000,00
Adresse
N PLASTIRA STR 100
70013 Irakleio
Grèce

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Région
Νησιά Αιγαίου Κρήτη Ηράκλειο
Type d’activité
Research Organisations
Contact administratif
Zinovia Papatheodorou (Ms.)
Liens
Coût total
Aucune donnée